1,075 research outputs found

    The Establishment of State Intermediate Education in France

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    There exists no historical conspectus of French intermediate education; and without that, it is impossible to appreciate its true relation to the present state system. In supplying that want, this study incidentally makes a contribution to the wider question of the limitations inherent in state action. Moreover, previous treaties, whether by official observers or private publicists, have been static in character, sumarising current legislation and statistics, but failing to show intermediate as a living growth, or to bring out its social implications. Our endeavour to make good those defects has led us to seek the roots of the official structure in society and the schools themselves; and in so doing, we have established an Anglo-French link which has completely escaped previous notice

    Regulation of signal transduction by RGS4

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    In the present study, the function and the mechanism of action of RGS4, a member of a family of proteins called Regulators of G protein Signalling (RGS) was investigated. A C-terminal fluorescent tag on RGS4 confirmed that transiently transfected RGS4 was predominantly cytosolic and underwent translocation to the plasma membrane of HEK293T cells following co-expression of Gi1, the 2A-adrenoceptor, or agonist activated 2A-adrenoceptor. This translocation of RGS4 to the plasma membrane was most pronounced with the co-expression of the constitutively active GTPase deficient Gi1 Q204L. High-affinity GTPase experiments indicated that RGS4S30C had enhanced GAP activity towards Go1 compared to wild type RGS4. This approach also demonstrated a simultaneous significant decrease in potency of both adrenaline and UK14304 to increase 2A-arenoceptor-activated high-affinity GTPase activity of Go1 in the presence of RGS4 and a further significant decrease in potency of both ligands in the presence of RGS4S30C. This enhanced GAP activity and observed decrease in agonist potency was also transferable to RGS16, an RGS protein closely related to RGS4. The selectivity of the G subunit was also investigated. The enhanced GAP activity and simultaneous significant decrease in potency of adrenaline and UK14304 to increase 2A-arenoceptor-activated high-affinity GTPase activity of RGS4S30C and RGS16S30C was selective for Go1 over Gi1. RGS4S30K and RGS4S30F also demonstrated higher GAP activity than wild type RGS4 but no consensus side chain could be identified that conferred a specific enhancement or loss of GAP activity. The ability to inhibit intracellular calcium release by an activated 1b-adrenoceptor-G11 fusion protein was used in order to investigate the GAP activity of RGS4N88S, RGS4N128A and RGS4N88S,N128A. All three mutants had ablated GAP activity towards G11 and therefore failed to inhibit intracellular calcium release. A novel role for the RGS insensitive mutation G188S was also observed when despite similar expression, G11 G188S significantly reduced agonist-stimulated [35S]GTPS binding compared to wild type G11. RGS4 represents a novel target for pharmaceutical drug development and the study of its regulation of signal transduction is an important area of investigation. These results highlight specific areas of RGS4 research with great pharmaceutical potential

    Sediment management for Southern California mountains, coastal plains and shoreline

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    The Environmental Quality Laboratory at Caltech and the Shore Processes Laboratory at Scripps Institution of Oceanography have jointly undertaken a study of regional sediment balance problems in coastal southern California (see map in Figure 1). The overall objective in this study is to define specific alternatives in sediment management that may be implemented to alleviate a) existing sediment imbalance problems (e.g. inland debris disposal, local shoreline erosion) and b) probable future problems that have not yet manifested themselves. These alternatives will be identified through a consideration of economic, legal, and institutional issues as well as an analysis of governing physical processes and engineering constraints. The first part of this study (Phase I), which is currently under way, involves a compilation and analysis of all available data in an effort to obtain an accurate definition of the inland/coastal regional sediment balance under natural conditions, and specific quantitative effects man-made controls have on the overall natural process. During FY77, substantial progress was made at EQL and SPL in achieving the objectives of the initial Planning and Assessment Phase of the CIT/SIO Sediment Management Project. Financial support came from Los Angeles County, U.S. Geological Survey, Orange County, U.S. Army Corps of Engineers, and discretionary funding provided by a grant from the Ford Foundation. The current timetable for completion of this phase is Fall 1978. This report briefly describes the project status, including general administration, special activities, and research work as of January 1978

    Three-point density correlation functions in the fractional quantum Hall regime

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    In this paper we consider the three-particle density correlation function for a fractional quantum Hall liquid. The study of this object is motivated by recent experimental studies of fractional quantum Hall systems using inelastic light scattering and phonon absorption techniques. Symmetry properties of the correlation function are noted. An exact sum-rule is derived which this quantity must obey. This sum-rule is used to assess the convolution approximation that has been used to estimate the matrix elements for such experiments. PACS Numbers: 73.40.Hm, 73.20.Mf, 72.10.DiComment: 12 pages + 1 (PS) figur

    Effects of dams on beach sand supply

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    In 1975 a regional sediment management study was initiated as a joint applied research project of the Environmental Quality Laboratory, California Institute of Technology, and the Shore Processes Laboratory, Scripps Institution of Oceanography. The project is a broad-based, long-term multidisciplinary effort intended to define the regional sediment budget for coastal Southern California (Figure 1), and to quantify the effects of various human activities on changes in that budget

    Genetic Characterization of the Tick-Borne Orbiviruses

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    The International Committee for Taxonomy of Viruses (ICTV) recognizes four species of tick-borne orbiviruses (TBOs): Chenuda virus, Chobar Gorge virus, Wad Medani virus and Great Island virus (genus Orbivirus, family Reoviridae). Nucleotide (nt) and amino acid (aa) sequence comparisons provide a basis for orbivirus detection and classification, however full genome sequence data were only available for the Great Island virus species. We report representative genome-sequences for the three other TBO species (virus isolates: Chenuda virus (CNUV); Chobar Gorge virus (CGV) and Wad Medani virus (WMV)). Phylogenetic comparisons show that TBOs cluster separately from insect-borne orbiviruses (IBOs). CNUV, CGV, WMV and GIV share low level aa/nt identities with other orbiviruses, in 'conserved' Pol, T2 and T13 proteins/genes, identifying them as four distinct virus-species. The TBO genome segment encoding cell attachment, outer capsid protein 1 (OC1), is approximately half the size of the equivalent segment from insect-borne orbiviruses, helping to explain why tick-borne orbiviruses have a ~1 kb smaller genome

    Adenylate cyclase activity during modulation of Bordetella pertussis

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    During the phenotypic and genotypic changes which occur during the processes respectively known as C modulation and phase degradation, several virulence-associated properties of Bordetella pertussis and adenylate cyclase (AC) are lost (Parton and Durham, 197B; Wardlaw and Parton, 1979). The main aim of the present investigation was to assess whether AC plays a causal role in these two distinct processes as this enzyme is known to play a key regulatory role in the Enterobacteriaceas. Growth of B. pertussis in Stainer and Scholte medium (SS-X) containing high levels of MgSO4, Na2 504, butyrate, Na caprylate, Na succinate or nicotinic acid resulted in C modulation as shown by marked reductions in AC activity, histamine-sensitizing activity (HSA) and the 28k and 3Dk cell-envelope polypeptides (X polypeptides). Although there was some variation between the susceptibility of strains to pro-C-mode salts, there was no instance of components being lost independently of each other. The level of cAMP in the supernate of C-mode cultures was less than 5x of that of X-inode cultures. Magnesium chloride, present at four times the molar concentration of MgSO4 required to induce C modulation, was ineffective at inducing loss of AC activity HSA, or the X polypeptides. During MgSO4-induced modulation, AC activity in three compartments (viz. culture supernate, cell-associated but extracytoplasmic, and cytoplasmic) was reduced to the same extent. Time-course studies on the rate of loss of AC activity, HSA, and the X-polypeptides during ngSO4-induced modulation indicated that these properties were lost simultaneously. Furthermore, losses could be accounted for by complete repression of the synthesis of the components when cells were introduced into C-medium. The low levels of cAMP in the supernate of C-mode cultures could not be accounted for by the ability of pro-C-mode salts to inhibit vitro AC activity, or by inhibition of cAMP excretion by C medium. Loss of AC activity during C modulation required growth and was not due to prolonged exposure to C medium, as chloramphenicol added to C medium prevented loss of AC activity. Loss of HSA and the X polypeptides also required growth or protein synthesis. C-mode cell lysate did not inhibit AC activity of X-mode cell lysate suggesting that loss of AC activity during C modulation is not due to production of an inactivating or inhibitory factor. Similarly, C-mode cell lysate did not destroy HSA present in X-mode cell lysate. Sodium fluoride caused marked inhibition of vitro AC activity, but, at the same concentration, had little effect on the synthesis of cAMP during growth. Growth in X medium containing B. pertussis AC activator (calmodulin) resulted in a four fold-increase in culture supernate cAMP levels. The critical concentration of MgSO4 required to induce loss of the X polypeptides was 10 - 11 mH. In one culture, containing 10 mH MgSD4 and AC activator, partial loss of the X polypeptides occurred yet cAMP levels in the supernate were twice that which normally occurred in X-mode cultures without activator. Respiration rates of amino acids by B. pertussis variants was investigated to determine whether cARP played a role in amino acid catabolism in the organism. The ability of washed suspensions of X- and C-mode and phase IV B. pertussis to respire L-glutamate, L-aspartate, L-proline, L-alanine and L-serine was demonstrated. While differences were found between the respiration rates of different amino acids, there were no significant differences between the ability of variants of B. pertussis to respire any particular amino acid. Phosphonomycin resistance has been used as a convenient method to isolate AC mutants of Escherichia coli. However, eight independently isolated phosphonomycin resistant mutants of B. pertussis possessed the same AC activity as the original strain. Exogenous cAMP and dibutyryl cAnP, in X and C media, had no effect on the production of AC, the X polypeptides or haeraagglutinin. Attempts were made to determine if a cyclic AnP-receptor protein (CRP) analogous to that in E. coli exists in B, pertussis. [3h] cAMP binding activity was demonstrated in several strains of B. pertussis and was about half that obtained for E. coli. Anti-E. coli CRP gave two precipitin lines with E. coli cell extract but none with B. pertussis cell extract. In conclusion, the results of this study suggest that AC does not play a causal role in modulation, and that the mechanism responsible for repressing synthesis of X-mode specific components (such as pertussigen) during modulation, also represses synthesis of AC

    Wolbachia-Mediated Antibacterial Protection and Immune Gene Regulation in Drosophila

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    The outcome of microbial infection of insects is dependent not only on interactions between the host and pathogen, but also on the interactions between microbes that co-infect the host. Recently the maternally inherited endosymbiotic bacteria Wolbachia has been shown to protect insects from a range of microbial and eukaryotic pathogens. Mosquitoes experimentally infected with Wolbachia have upregulated immune responses and are protected from a number of pathogens including viruses, bacteria, Plasmodium and filarial nematodes. It has been hypothesised that immune upregulation underpins Wolbachia-mediated protection. Drosophila is a strong model for understanding host-Wolbachia-pathogen interactions. Wolbachia-mediated antiviral protection in Drosophila has been demonstrated for a number of different Wolbachia strains. In this study we investigate whether Wolbachia-infected flies are also protected against pathogenic bacteria. Drosophila simulans lines infected with five different Wolbachia strains were challenged with the pathogenic bacteria Pseudomonas aeruginosa PA01, Serratia marcescens and Erwinia carotovora and mortality compared to paired lines without Wolbachia. No difference in mortality was observed in the flies with or without Wolbachia. Similarly no antibacterial protection was observed for D. melanogaster infected with Wolbachia. Interestingly, D. melanogaster Oregon RC flies which are naturally infected with Wolbachia showed no upregulation of the antibacterial immune genes TepIV, Defensin, Diptericin B, PGRP-SD, Cecropin A1 and Attacin D compared to paired flies without Wolbachia. Taken together these results indicate that Wolbachia-mediated antibacterial protection is not ubiquitous in insects and furthermore that the mechanisms of antibacterial and antiviral protection are independent. We suggest that the immune priming and antibacterial protection observed in Wolbachia-infected mosquitoes may be a consequence of the recent artificial introduction of the symbiont into insects that normally do not carry Wolbachia and that antibacterial protection is unlikely to be found in insects carrying long-term Wolbachia infections

    Enhanced neutralising antibody response to bovine viral diarrhoea virus (BVDV) induced by DNA vaccination in calves

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    DNA vaccination is effective in inducing potent immunity in mice; however it appears to be less so in large animals. Increasing the dose of DNA plasmid to activate innate immunity has been shown to improve DNA vaccine adaptive immunity. Retinoic acid-inducible gene I (RIG-I) is a critical cytoplasmic double-stranded RNA pattern receptor required for innate immune activation in response to viral infection. RIG-I recognise viral RNA and trigger antiviral response, resulting in type I interferon (IFN) and inflammatory cytokine production. In an attempt to enhance the antibody response induced by BVDV DNA in cattle, we expressed BVDV truncated E2 (E2t) and NS3 codon optimised antigens from antibiotic free-plasmid vectors expressing a RIG-I agonist and designated either NTC E2t(co) and NTC NS3(co). To evaluate vaccine efficacy, groups of five BVDV-free calves were intramuscularly injected three times with NTC E2t(co) and NTC NS3(co) vaccine plasmids individually or in combination. Animals vaccinated with our (previously published) conventional DNA vaccines pSecTag/E2 and pTriExNS3 and plasmids expressing RIG-I agonist only presented both the positive and mock-vaccine groups. Our results showed that vaccines coexpressing E2t with a RIG-I agonist induced significantly higher E2 antigen specific antibody response (p < 0.05). Additionally, E2t augmented the immune response to NS3 when the two vaccines were delivered in combination. Despite the lack of complete protection, on challenge day 4/5 calves vaccinated with NTC E2t(co) alone or NTC E2t(co) plus NTC NS3(co) had neutralising antibody titres exceeding 1/240 compared to 1/5 in the mock vaccine control group. Based on our results we conclude that co-expression of a RIG-I agonist with viral antigen could enhance DNA vaccine potency in cattle

    Magnetoroton scattering by phonons in the fractional quantum Hall regime

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    Motivated by recent phonon spectroscopy experiments in the fractional quantum Hall regime we consider processes in which thermally excited magnetoroton excitations are scattered by low energy phonons. We show that such scattering processes can never give rise to dissociation of magnetorotons into unbound charged quasiparticles as had been proposed previously. In addition we show that scattering of magnetorotons to longer wavelengths by phonon absorption is possible because of the shape of the magnetoroton dispersion curve and it is shown that there is a characteristic cross-over temperature above which the rate of energy transfer to the electron gas changes from an exponential (activated) to a power law dependence on the effective phonon temperature.Comment: LaTex document, 3 eps figures. submitted to Phys Rev
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